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Neurosci Bull. 2016 Feb;32(1):99-107. doi: 10.1007/s12264-015-0003-8. Epub 2016 Jan 15.

TNP-ATP is Beneficial for Treatment of Neonatal Hypoxia-Induced Hypomyelination and Cognitive Decline.

Author information

1
Department of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University, Kunming, 650500, China.
2
Department of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University, Kunming, 650500, China. leefan623@sina.com.

Abstract

Our previous study together with other investigations have reported that neonatal hypoxia or ischemia induces long-term cognitive impairment, at least in part through brain inflammation and hypomyelination. However, the detailed mechanisms are not fully understood. Here, we used a rodent model of neonatal hypoxia by subjecting postnatal day 0 (P0) rat pups to systemic hypoxia (3.5 h). We found that neonatal hypoxia increased the glutamate content and initiated inflammatory responses at 4 h and 1 day after hypoxia, caused hypomyelination in the corpus callosum, and impaired hippocampus-dependent learning and memory when assessed 30-60 days after hypoxia. Interestingly, much of the hypoxia-induced brain damage was ameliorated by treatment with the ATP analogue 2',3'-0-(2,4,6-trinitrophenyl)-adenosine 5'-triphosphate (TNP-ATP; blocks all ionotropic P2X1-7 receptors), whereas treatment with pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; inhibits P2X1-3 and P2X5-7 receptors) was less neuroprotective. Our data indicated that activation of ionotropic ATP receptors might be partially, if not fully, involved in glutamate deregulation, neuroinflammation, hypomyelination, and cognitive dysfunction after neonatal hypoxia.

KEYWORDS:

Glutamate; Inflammation; Ionotropic ATP receptors; Memory deficit; Neonatal hypoxia

PMID:
26769489
PMCID:
PMC5563748
DOI:
10.1007/s12264-015-0003-8
[Indexed for MEDLINE]
Free PMC Article

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